Adiponectin regulates white adipose tissue (WAT) metabolism and promotes insulin-sensitizing and anti-atherosclerotic effects in vivo. In this context, small molecule adiponectin receptor agonists have become of great therapeutic value for the treatment of metabolic diseases. Here, we investigated the effects of the adiponectin mimetic compound ALY688 on WAT metabolism. To accomplish this, rat epididymal (Epid) and subcutaneous inguinal (Sc Ing) adipocytes were isolated and incubated with ALY688. Subsequently, several parameters of glucose and fat metabolism were assessed. ALY688 promoted AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, enhanced glucose oxidation, and suppressed fat oxidation in adipocytes from both fat depots. ALY688 did not affect basal and insulin-stimulated rates of glucose uptake, glucose incorporation into lipids, and AKT_Ser473 and p38 mitogen-activated protein kinase (MAPK) phosphorylations in either Epid or Sc Ing adipocytes. ALY688 did not alter basal lipolysis in Epid and Sc Ing adipocytes, but it enhanced isoproterenol-induced lipolysis in Epid adipocytes. Adiponectin receptor 2 (AdipoR2) mRNA was the prevalent isoform expressed in all adipocytes, and Epid adipocytes displayed significantly higher AdipoR2 mRNA expression than Sc Ing adipocytes. In conclusion, ALY688 can regulate adiposity and affect glycaemic control by altering substrate portioning in the WAT in a fat depot-specific manner.

脂联素在体内调节白色脂肪组织（WAT）的代谢并促进胰岛素敏感性和抗动脉粥样硬化作用。在这种情况下，小分子脂联素受体激动剂已对代谢疾病的治疗具有重要的治疗价值。在这里，我们调查了脂联素模拟化合物ALY688对WAT代谢的影响。为此，分离大鼠附睾（Epid）和腹股沟皮下（Sc Ing）脂肪细胞，并与ALY688孵育。随后，评估了葡萄糖和脂肪代谢的几个参数。ALY688促进了AMP激活的蛋白激酶（AMPK）和乙酰辅酶A羧化酶（ACC）的磷酸化，增强了葡萄糖的氧化作用，并抑制了来自两个脂肪库的脂肪细胞中的脂肪氧化。ALY688不会影响基础和胰岛素刺激的葡萄糖摄取率，葡萄糖掺入脂质和AKT _Ser473的速率Epid或Sc Ing脂肪细胞中的p38丝裂原活化蛋白激酶（MAPK）磷酸化。ALY688不会改变Epid和Sc Ing脂肪细胞的基础脂解作用，但会增强异丙肾上腺素诱导的Epid脂肪细胞的脂解作用。脂联素受体2（AdipoR2）mRNA是在所有脂肪细胞中表达的普遍同工型，而Epid脂肪细胞显示的Sdig脂肪细胞中AdipoR2 mRNA的表达明显更高。总之，ALY688可以通过改变脂肪仓库中WAT的底物比例来调节肥胖并影响血糖控制。